Next Article in Journal
GC–MS-Based Nontargeted and Targeted Metabolic Profiling Identifies Changes in the Lentinula edodes Mycelial Metabolome under High-Temperature Stress
Next Article in Special Issue
Effect of Peritoneal Dialysis on Serum Fibrosis Biomarkers in Patients with Refractory Congestive Heart Failure
Previous Article in Journal
Non-Linear Quantitative Structure–Activity Relationships Modelling, Mechanistic Study and In-Silico Design of Flavonoids as Potent Antioxidants
Previous Article in Special Issue
Changes of Circulating Extracellular Vesicles from the Liver after Roux-en-Y Bariatric Surgery
Article Menu
Issue 9 (May-1) cover image

Export Article

Open AccessArticle

Multiple Glycation Sites in Blood Plasma Proteins as an Integrated Biomarker of Type 2 Diabetes Mellitus

1
Department of Biochemistry, St. Petersburg State University, 199034 Saint Petersburg, Russia
2
Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, D-06120 Halle (Saale), Germany
3
Almazov National Medical Research Centre, 197341 Saint Petersburg, Russia
4
Department of Faculty Therapy, The First Pavlov St. Petersburg State Medical University, 197022 Saint Petersburg, Russia
5
Proteome Analytics Research Group, Leibniz Institute of Plant Biochemistry, D-06120 Halle (Saale), Germany
6
Institute of Pharmacy, Martin Luther University of Halle-Wittenberg, D-06120 Halle (Saale), Germany
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(9), 2329; https://doi.org/10.3390/ijms20092329
Received: 15 March 2019 / Revised: 14 April 2019 / Accepted: 7 May 2019 / Published: 10 May 2019
(This article belongs to the Special Issue Molecular Research on Metabolic Disorders)
  |  
PDF [3895 KB, uploaded 10 May 2019]
  |     |  

Abstract

Type 2 diabetes mellitus (T2DM) is one of the most widely spread metabolic diseases. Because of its asymptomatic onset and slow development, early diagnosis and adequate glycaemic control are the prerequisites for successful T2DM therapy. In this context, individual amino acid residues might be sensitive indicators of alterations in blood glycation levels. Moreover, due to a large variation in the half-life times of plasma proteins, a generalized biomarker, based on multiple glycation sites, might provide comprehensive control of the glycemic status across any desired time span. Therefore, here, we address the patterns of glycation sites in highly-abundant blood plasma proteins of T2DM patients and corresponding age- and gender-matched controls by comprehensive liquid chromatography-mass spectrometry (LC-MS). The analysis revealed 42 lysyl residues, significantly upregulated under hyperglycemic conditions. Thereby, for 32 glycation sites, biomarker behavior was demonstrated here for the first time. The differentially glycated lysines represented nine plasma proteins with half-lives from 2 to 21 days, giving access to an integrated biomarker based on multiple protein-specific Amadori peptides. The validation of this biomarker relied on linear discriminant analysis (LDA) with random sub-sampling of the training set and leave-one-out cross-validation (LOOCV), which resulted in an accuracy, specificity, and sensitivity of 92%, 100%, and 85%, respectively. View Full-Text
Keywords: Amadori compounds; biomarkers; glycation; glycation sites; label-free quantification; linear discriminant analysis; mass spectrometry; plasma proteins; type 2 diabetes mellitus Amadori compounds; biomarkers; glycation; glycation sites; label-free quantification; linear discriminant analysis; mass spectrometry; plasma proteins; type 2 diabetes mellitus
Figures

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material

SciFeed

Share & Cite This Article

MDPI and ACS Style

Soboleva, A.; Mavropulo-Stolyarenko, G.; Karonova, T.; Thieme, D.; Hoehenwarter, W.; Ihling, C.; Stefanov, V.; Grishina, T.; Frolov, A. Multiple Glycation Sites in Blood Plasma Proteins as an Integrated Biomarker of Type 2 Diabetes Mellitus. Int. J. Mol. Sci. 2019, 20, 2329.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top